Hydroxylamines are an interesting group of compounds if only because they contain two nucleophilic atoms, nitrogen and oxygen, bonded to each other. Indeed, either of the nucleophilic atoms can take part in nucleophilic reactions, depending upon the reactants and substrates. Still further, the nucleophilicity of hydroxylamines is enhanced over that expected on the basis of their pK.sub.a values in what has been termed the ".alpha.-effect" [Edwards et al., J. Am. Chem. Soc., 84:16 (1962)].
Aliphatic primary hydroxyl amines; i.e., a hydroxylamine substituted on the nitrogen atom by a single aliphatic organic radical, such as N-methyl hydroxylamine are items of commerce. N-Acylated hydroxyl amines form hydroxamic acids, which can be used in assays for the presence of iron.sup.III ions because of the reddish colored complexes that are formed. Primary hydroxylamines also act as ligands to form complexes with metal ions.
Primary hydroxylamines are typically prepared by reaction of hydroxylamine itself with an aldehyde to form an oxime, followed by reduction of the oxime with a mild reducing agent. Primary amines oxidized with Caro's acid (H.sub.2 SO.sub.5) typically form the corresponding nitrone that rearranges to an oxime, with the hydroxylamine being a postulated intermediate. Secondary amines oxidized with Caro's acid form secondary hydroxylamines.
The usual .alpha.-amino acids are also used as ligands to complex with metal ions such as iron. The corresponding .alpha.-hydroxylamino acids, and their corresponding hydroximates are also useful as ligands for forming complexes with metal ions such as Fe.sup.III.
The recently reported calicheamicin [see, Lee et al., J. Am. Chem. Soc., 109:3464 (1987) and the citations therein] and esperamicin [see, (a) Golik et al., J. Am. Chem. Soc., 109:3461 (1987); and (b) Golik et al., J. Am. Chem. Soc., 109:3462 (1987) and the citations therein] antibiotics contain a novel hydroxylamine-substituted glycosidic unit in their oligosaccharide side chains. Inasmuch as the polysaccharide portions of the calicheamicins and esperamicins appear to direct those antibiotics to DNA molecules where they intercalate and cleave the DNA, it would be of interest to synthesize the hydroxylamine-containing sugar derivatives as well as the entire oligosaccharide portion of an esperamicin or a calicheamicin that could be then bonded to the enediyne portion to form a synthetic esperamicin or calicheamicin or derivative thereof.
It would therefore be beneficial if a relatively high yielding, simple synthesis could be devised to form aliphatic primary hydroxylamine compounds. The disclosure below describes one such process for the preparation of aliphatic primary hydroxylamine compounds.